CED-10/Rac1 regulates endocytic recycling through the RAB-5 GAP TBC-2

PLoS Genet. 2012;8(7):e1002785. doi: 10.1371/journal.pgen.1002785. Epub 2012 Jul 12.


Rac1 is a founding member of the Rho-GTPase family and a key regulator of membrane remodeling. In the context of apoptotic cell corpse engulfment, CED-10/Rac1 acts with its bipartite guanine nucleotide exchange factor, CED-5/Dock180-CED-12/ELMO, in an evolutionarily conserved pathway to promote phagocytosis. Here we show that in the context of the Caenorhabditis elegans intestinal epithelium CED-10/Rac1, CED-5/Dock180, and CED-12/ELMO promote basolateral recycling. Furthermore, we show that CED-10 binds to the RAB-5 GTPase activating protein TBC-2, that CED-10 contributes to recruitment of TBC-2 to endosomes, and that recycling cargo is trapped in recycling endosomes in ced-12, ced-10, and tbc-2 mutants. Expression of GTPase defective RAB-5(Q78L) also traps recycling cargo. Our results indicate that down-regulation of early endosome regulator RAB-5/Rab5 by a CED-5, CED-12, CED-10, TBC-2 cascade is an important step in the transport of cargo through the basolateral recycling endosome for delivery to the plasma membrane.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / metabolism
  • Caenorhabditis elegans* / physiology
  • Carrier Proteins / metabolism
  • Cell Membrane / metabolism
  • Cytoskeletal Proteins / metabolism
  • Endocytosis* / genetics
  • Endocytosis* / physiology
  • Endosomes / metabolism
  • Endosomes / physiology
  • GTPase-Activating Proteins* / genetics
  • GTPase-Activating Proteins* / metabolism
  • Gene Expression Regulation
  • Intestinal Mucosa / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutation
  • Phagocytosis / genetics
  • Protein Transport
  • Signal Transduction
  • Vesicular Transport Proteins* / genetics
  • Vesicular Transport Proteins* / metabolism
  • rac GTP-Binding Proteins* / genetics
  • rac GTP-Binding Proteins* / metabolism


  • Apoptosis Regulatory Proteins
  • CED-10 protein, C elegans
  • CED-12 protein, C elegans
  • CED-5 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • GTPase-Activating Proteins
  • Membrane Proteins
  • Rab-5 protein, C elegans
  • TBC-2 protein, C elegans
  • Vesicular Transport Proteins
  • rac GTP-Binding Proteins